The potential of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to initiate and/or promote tumorigenesis is being evaluated. Fifty male and 50 female rats have been fed diets containing 500 parts per trellion (ppt) TCDD for 15 months to date. An equal number of control animals will be evaluated for spontaneous tumors. In addition, 50 male rats treated with diethylnitrosamine for 5 weeks have been placed on a diet containing 500 ppt TCDD. This latter study is designed to show whether or not TCDD can promote hepatic tumors in animals treated with hepatocarcinogens. Studies on the toxicity of TCDD to cells inculture are in progress. The hydrophobic nature of TCDD has mandated using unconventional techniques to add the compound to cell cultures. Currently artificial lipid membranes (i.e. liposomes) are being tried as carriers for TCDD. Several toxicity and transformation studies are planned when the solubility problem is solved. In addition, experiments in which cell populations (e.g. liver and thymus) will be isolated from rats treated with TCDD are scheduled. Due to the apparent lack of metabolism chemical interactions of TCDD with cell components are being evaluated. Initially these studies will test membrane effects since TCDD is associated with microsomes in vivo. All of the parameters will be evaluated both in vivo and in vitro. Microsomal membranes and plasma membranes will be tested for association of TCDD by electrophoresis. Alterations in membrane structure will be evaluated using differential scanning calorimetry. Active and passive transport will be examined. In addition, the integrity of membrane enzyme markers including Mg ATPase and nucleotidase will be tested.